Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

背景：全世界数以亿计的患者和90万美国人正在遭受肝纤维化/肝硬变的困扰。 肝活检是目前诊断肝纤维化的金标准，是侵入性的，偶尔可能 造成重大并发症，这限制了对高危人群的筛查、治疗监测和 后续行动。目前的血清标志物和经典的医学成像，如超声、CT或MRI，没有 对纤维化评估有足够的灵敏度/特异度。最近的研究表明，组织弹性(即硬度) 可用于肝纤维化分期。在此，我们提出了一种新的超声方法--剪切波超声 色散测振法(SDUV)，用于非侵入性、活检式的弹性和粘度量化 肝纤维化分期。方法：SDUV使用FDA安全范围内的超声波“推”射束进行刺激 在所研究的组织中形成传播的简谐横波。诱导剪切的传播速度 波是频率相关的(频散)，与组织的机械特性有关。横波 多个频率(通常为数百赫兹)的速度由单独的超声波“检测”来测量。 光束为脉冲回波模式，并与理论色散模型拟合，以反向求解组织弹性和 粘度。在组织模体和横纹肌方面的初步研究非常有前途。一份特别的 已经开发了脉冲序列以便于用于推送和检测的单个超声阵列换能器 功能，使SDUV与目前的超声波扫描仪兼容。该脉冲序列的可行性 已经通过使用内部仪器在正常猪肝脏中的活体测量进行了验证。目标：1. 在商用超声扫描仪上实现SDUV。2.使用体模对样机进行标定和优化。 体外组织实验和活体动物实验。3.对疑似患者进行临床研究 计划接受临床指征的肝活检的肝纤维化患者。成功完成这项工作 该项目将产生一种新的临床技术--SDUV，以实现无创、快速、经济和可靠的虚拟 活检“用于纤维化分期。

Background: Liver fibrosis/cirrhosis afflicts hundreds of millions of patients worldwide and 900,000 Americans. Liver biopsy, currently the gold standard for the diagnosis of liver fibrosis, is invasive and may occasionally cause significant complications, which limits the screening of at-risk populations, treatment monitoring, and follow-up. Current serum markers and classic medical imaging such as ultrasound, CT, or MRI do not have sufficient sensitivity/specificity for fibrosis evaluation. Recent studies show that tissue elasticity (i.e. stiffness) may be used for liver fibrosis staging. Herein we propose a novel ultrasound method, Shearwave Ultrasound Dispersion Vibrometry (SDUV), for noninvasive, biopsy-like quantification of elasticity as well as viscosity for liver fibrosis staging. Method: SDUV uses an ultrasound "push" beam within FDA safety limits to stimulate formation of propagating harmonic shear waves in the studied tissue. The propagation speed of induced shear waves is frequency dependent (dispersive) and relates to the tissue's mechanical properties. Shear wave speeds at multiple frequencies (typically hundreds of Hertz) are measured by a separate ultrasound "detect" beam in pulse echo mode and fit with a theoretical dispersion model to inversely solve for tissue elasticity and viscosity. Preliminary studies in tissue-mimicking phantom and striated muscle are very promising. A special pulse sequence has been developed to facilitate a single ultrasound array transducer for both push and detect function, which makes SDUV compatible with current ultrasound scanners. Feasibility of this pulse sequence has been validated with in vivo measurements in normal porcine liver using in-house instrumentation. Aims: 1. Implement SDUV on a commercial ultrasound scanner. 2. Calibrate and optimize the prototype with phantom, in vitro tissue, and in vivo animal experiments. 3. Conduct a clinical research on patients with suspected hepatic fibrosis who are scheduled to have a clinically indicated liver biopsy. Successful completion of this project should result in a new clinical technique, SDUV, for noninvasive, fast, economical, and reliable "virtual biopsy" for fibrosis staging.